Tuberculosis (TB) suspect is any one who has signs or symptoms suggestive of TB (eg >2 weeks productive cough).
Definite TB is considered in patients with culture or molecular line probe assay positive for Mycobacterium tuberculosis, or in patients with at least 1 sputum smear positive for acid-fast bacilli.
TB cases are also classified based on the disease anatomical site, bacteriological results (including drug resistance), previous treatment history and patient's HIV status.
Pulmonary TB is a case of TB that involves the lung parenchyma.
Miliary TB is considered as PTB since lung lesions are also seen.
TB in the pleural effusion, mediastinal and/or hilar lymph nodes with no evidence of abnormalities in the chest x-ray are considered extrapulmonary TB.
Patients presenting with both PTB and extrapulmonary TB are classified as a case of PTB.

Acquired resistance occurs during therapy when resistance to >1 drug develops in organisms that were initially susceptible to the drugs

Best way to prevent is to use at least 2 bactericidal drugs to which the organisms are sensitive & to employ daily intensive-phase dosing especially in TB patients starting treatment w/ Isoniazid resistance

In individuals with drug-susceptible PTB, daily intake of the required medications is recommended & the thrice-weekly regimen is no longer advisable, both in the intensive & continuation phases

Twice-weekly dosing is no longer recommended because of increase in noncompliance rate

Thrice-weekly dosing is also no longer recommended since:

Studies showed that when daily regimen was compared to thrice-weekly regimen throughout the duration of treatment, TB recurrence, failure in therapy & acquired drug resistance were all higher in the latter

When daily regimen was compared to thrice-weekly regimen in the continuation phase, TB recurrence & failure in therapy were seen more in the latter, however, there was no difference when it comes to acquired drug resistance, hence, if thrice-weekly regimen is to be used in the continuation phase, it is important that the patient is under DOT, & that medications are taken without fail

Poor compliance to anti-TB regimen is the most common cause of treatment failure

Part of the patient-centered care adherence plan

Helpful way to monitor adherence of patient to therapy

Process where a health care worker watches the patient to swallow each dose of the drug to ensure that completion of treatment is achieved

Ideally prevents the emergence of drug resistance when a suitable regimen is given

DOT given at home or in the local municipal area is preferred rather than in a health care institution

DOT facilitated by health care practitioners or lay people who underwent training are preferred than those provided by relatives & those that are self-administered

Video-observed Therapy (VOT)

Advantages include: Compliance is observed even if the patient is far away, more convenient with regards to schedules, less expenses & can be used as an alternative or as an adjunct with other types of treatment administration

Decentralized Versus Centralized Model of Care

Decentralized care

Recommended for MDR-TB patients, including those who were hospitalized for <1 month for treatment initiation or management of complications

That which is centered in the local district area, wherein care is delivered in health care centers by general physicians, community-based health care workers & volunteers

May not be applicable for certain groups of patients, such as those with severe or highly infectious TB, with concomitant medical disorders, or non-compliant patients

Practices under this type of care should not hinder the need for hospitalization

Centralized care

Carried out by hospitals & specialized institutions or clinics particularly allocated for drug-resistant TB patients, facilitated by physicians or other health care providers with specialty in this field

Implemented during the intensive phase of treatment or until culture or smear conversion

Treatment Interruption

If patient misses a treatment, the NTP should contact the patient

Within a day after missing treatment during the initial phase

Within a week if during the continuation phase

Culture & DST should be done upon return of the patient who missed 2 consecutive months of treatment

Hospitalization

Recommended in severely ill patients & for those w/ complications of the disease or its treatment that need closer clinical monitoring

May also be considered in patients during the intensive phase for whom there are no other means of ensuring treatment adherence & support

Pharmacotherapy

Treatment Regimen for New Tuberculosis (TB) Patients

Therapy consists of 1st-line anti-TB agents

In patients with drug-susceptible PTB, the 6-month Rifampicin-based therapy 2HRZE/4HR is the preferred treatment & the 4-month fluoroquinolone-containing therapy should be avoided

Intensive phase is defined by the duration of treatment with the injectable agents

Injectable agents should be continued for a minimum of 6 months & for at least 4 months after the patient had smear & culture conversion

Therapy should be continued for a minimum of 18 months until after culture conversion

Therapy may be extended for up to 24 months in patients with extensive pulmonary damage

Individuals diagnosed to have MDR-TB or RR-TB who are identified to have absence of resistance to fluoroquinolones & 2nd-line injectable agents or are regarded as having such resistance improbable & did not have prior 2nd-line drug treatment may have a shorter duration of MDR-TB therapy of 9-12 months

Shorter MDR-TB therapy is not advisable in patients who received treatment with 2nd-line drugs for >1 month & those with extrapulmonary disease

The following may follow the short-term regimen: Adult & children diagnosed with RR-TB without MDR-TB, even without documented resistance to Isoniazid; patients free from resistance to the medications used in the shorter regimen & non-pregnant women

Children & patients with HIV can be regarded with the same consideration as adults & people without HIV, respectively, in terms of using the shorter regimen

For the longer regimen, individuals diagnosed to have MDR-TB or RR-TB are required in the intensive phase to take at least 5 TB drugs, which are composed of the following: Pyrazinamide, 1 drug from group A, 1 drug from group B & 2 drugs from group C

If the recommended number is not met, drugs from group D2 or D3 can compensate for the lack of required number in order to complete the 5 drugs recommended

May consider addition of agents from group C or D if Pyrazinamide treatment cannot be tolerated

High-dose Isoniazid &/or Ethambutol may be considered in individuals with MDR-TB or RR-TB

ART is introduced in the therapy within the first 8 weeks after starting TB treatment

Introduced within the first 2 weeks after starting TB treatment only if the patient is significantly immunocompromised (eg CD4 cell count below 50 cells/mm3)

In those with concomittant TB meningitis, side effects that are more severe were observed when ART is introduced early than when it was initiated after 8 weeks (2 months) of TB therapy

For patients who have PTB, that is drug-susceptible & under ART therapy, a 6-month duration is preferred rather than 8-months or more with regards to TB treatment completion

Patients w/ Tuberculous Meningitis

Corticosteroid (Dexamethasone or Prednisolone) should be added in the treatment, tapered for 6-8 weeks

Patients w/ Tuberculous Pericarditis

Corticosteroid may also be added in the treatment

Patients w/ LTBI

Isoniazid-Rifapentine combination, administered weekly for 12 weeks (3 HP) is approved for adults, patients 2-17 years of age, those who are afflicted with HIV & acquired immunodeficiency syndrome (AIDS) & are under antiretroviral therapy which does not affect the actions of Rifapentine

Has narrow therapeutic index, thus dosage should not be lower than recommended dose

Pyrazinamide (Z)

Indicated for all forms of TB caused by organisms that are known or presumed to be susceptible

Only weakly bactericidal but has potent sterilizing activity, particularly in macrophages & in areas of acute inflammation

Highly effective against acute inflammatory changes during the first 2 months of treatment

Has shortened the treatment regimen & reduced the risk of relapse

Ethambutol (E)

Generally used in combination w/ other anti-TB agents to prevent/delay the emergence of resistant strains

Included in initial treatment regimen primarily to prevent emergence of Rifampicin resistance when primary resistance to Isoniazid may be present

Added to Isoniazid + Rifampicin continuation phase in patients from populations w/ known or suspected high levels of Isoniazid resistance & Isoniazid susceptibility testing is not done

2nd-Line Anti-Tuberculosis (TB) Agents

Should be used in patients w/ MDR-TB

Aminoglycosides

Belong to group B injectable agents for use in susceptible MDR-TB & RR-TB patients in longer treatment regimen

Eg Kanamycin, Amikacin, Capreomycin, Streptomycin

Considered 1st choice among the injectable agents for MDR-TB which has lower resistance, lower cost & less ototoxic side effect as compared to Streptomycin

Have been used extensively for the treatment of MDR-TB

Streptomycin (S)

An aminoglycoside antibiotic derived from Streptomyces griseus that is used for TB & gram-negative sensitive infections

Streptomycin & Ethambutol are approximately equivalent when used in the initial treatment phase but Streptomycin use may be limited based on local M tuberculosis resistance patterns

Has high resistance in drug-resistant TB

Streptomycin may be substituted if Ethambutol is contraindicated

Although it is not usually part of the 2nd-line agents in the long-term duration of MDR-TB therapy, it may be used instead if the other 3 drugs in group B are contraindicated

Not absorbed from the gastrointestinal (GI) tract but after intramuscular (IM) administration, it diffuses readily into the extracellular component of most body tissues & attains bactericidal concentrations, particularly in tuberculous cavities

Bedaquiline

Recently approved treatment for adult patients w/ pulmonary MDR-TB

May also be used in RR-TB

Given as part of the combination therapy for extensively drug-resistant TB (XDR-TB) & MDR-TB allergic to >2 drugs

In the revised grouping, it is currently under group D2, as part of the add-on medications for the longer regimen of MDR-TB & RR-TB treatment

May only be considered for immunocompromised patients (children, HIV-positive persons, pregnancy), patients w/ extrapulmonary TB, and those w/ comorbidities if other therapies are unavailable or ineffective

Delamanid

A nitro-dihydro-imidazooxazole that inhibits mycolic acid synthesis & has been recently approved for the treatment of MDR-TB

Given as part of the combination therapy for MDR-TB in adult patients who are intolerant or resistant to standard effective treatment regimen

D3: Para-aminosalicylic acid, Imipenem-cilastatin, Meropenem, Amoxicillin-clavulanate (Carbapenems & Clavulanate should be used concomitantly; Clavulanate is available only in combination with Amoxicillin), Thioacetazone (contraindicated in HIV patients)

Composed of agents that are not included in the core group of 2nd-line medications

Resistance of M tuberculosis to the macrolides (Clarithromycin, Azithromycin) enabled their removal in the list of agents for MDR-TB

Separate medications may be beneficial for certain individuals who have accompanying medical disorders (eg those with kidney or renal disease, drug intolerance) since each drug may need to undergo dose adjustment

≥2 drugs incorporated in a single tablet that reduces the number of pills that needs to be consumed

May prevent having drug resistance secondary to monotherapy

Advantageous since prescription errors may be less frequent because of more straightforward dosage recommendations, easier adjustment of dosage based on patient’s weight, & may promote patient’s compliance due to smaller number of tablets to consume

Some trials have shown that FDC & monotherapy are equally effective but FDC are more acceptable to patients

Does not prevent the need for separate drugs in patients who will develop drug toxicity or intolerance, or in patients w/ contraindication to individual drug component

Surgical Intervention

Elective partial lung resection (eg lobectomy, wedge resection), with an appropriate MDR-TB therapy may be utilized as a treatment approach in patients w/ MDR-TB or RR-TB